m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics

F Consolato, F Maltecca, S Tulli, I Sambri, G Casari

Research output: Contribution to journalArticle

Abstract

The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation ofmitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and autoproteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m)-AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m-AAA and i-AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena. © 2018. Published by The Company of Biologists Ltd.
Original languageEnglish
Article numberjcs213546
JournalJournal of Cell Science
Volume131
Issue number7
DOIs
Publication statusPublished - 2018

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Mitochondrial Dynamics
Peptide Hydrolases
Dynamins
Mitochondrial Diseases
GTP Phosphohydrolases
Consensus Sequence
Mitochondrial Membranes
Metalloproteases
Neurodegenerative Diseases
Zinc
Protein Isoforms

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m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics. / Consolato, F; Maltecca, F; Tulli, S; Sambri, I; Casari, G.

In: Journal of Cell Science, Vol. 131, No. 7, jcs213546, 2018.

Research output: Contribution to journalArticle

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AB - The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation ofmitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and autoproteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m)-AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m-AAA and i-AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena. © 2018. Published by The Company of Biologists Ltd.

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